Non-Myeloablative HLA-Mismatched Ex-Vivo T-cell Depleted Stem Cell Transplantation for Hematologic Malignancies
One major obstacle to further advancement in the role of bone marrow transplant (BMT) in
hematological malignancies is graft-versus-host-disease (GVHD), which can best be prevented
by removing T-cells from the donor stem cell product. However, previous experience with
T-cell depletion has been associated with an increased rate of engraftment failure and
leukemic relapse. Another obstacle is that a large fraction of leukemia and lymphomas
afflict older patients who are more prone to GVHD and have co-morbid conditions that prevent
them from being a candidate for BMT.
This trial uses a non-myeloablative conditioning regimen with cyclophosphamide, MEDI-507,
fludarabine, and thymic irradiation followed by a T-cell depleted PBSC infusion.
Cyclosporine is used for GVHD prophylaxis, and tapered beginning on day 35. Data from our
mouse model and previous clinical trials have demonstrated that this approach can induce
mixed chimerism without GVHD, with the potential for conversion of mixed chimerism to full
donor hematopoiesis following donor leukocyte infusions.
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To evaluate the risk of graft loss and severe GVHD or transplant related mortality at < 100 days following HLA-mismatched non-myeloablative stem cell transplantation.
Thomas Spitzer, M.D.
Massachusetts General Hospital, Harvard University
United States: Food and Drug Administration
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